The RAS/MEK/ERK signaling cascade positively regulates the transcriptional activity of glioma-associated oncogene homolog 1 (GLI1), a nuclear mediator of the Hedgehog pathway, thereby inducing the expression of hedgehog target genes in GC cells.508 Jayati et al. found that hedgehog signaling contributes to inducing PD-L1 expression in GC, and PD-1/PD-L1 inhibition reverses GLI2-induced tolerance, such that combined inhibition of hedgehog signaling and immune checkpoints may be suitable for selected patients.509. The gene discussed is CD274; the disease is gastric cancer.